Acta Biomaterialia最新文献

{"title":"Co-delivery of neurotrophic factors and a zinc chelator substantially increases retinal ganglion cell survival and axon protection in the optic nerve crush model","authors":"Huynh Quang Dieu Nguyen ,&nbsp;Mi-hyun Nam ,&nbsp;Jozsef Vigh ,&nbsp;Joseph Brzezinski ,&nbsp;Lucas Duncan ,&nbsp;Daewon Park","doi":"10.1016/j.actbio.2025.06.007","DOIUrl":"10.1016/j.actbio.2025.06.007","url":null,"abstract":"<div><div>Traumatic optic neuropathies lead to retinal ganglion cell (RGC) death and axonal degeneration, primarily due to disrupted neurotrophic factor (NTF) supply from the brain and a neurotoxic cascade, potentially mediated by elevated retinal Zn²⁺ levels. Ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) are two major NTFs known to support RGC survival and axon protection. Dipicolylamine (DPA), a Zn²⁺ chelator with high selectivity and affinity, offers a strategy to reduce excess Zn²⁺. To achieve sustained NTF delivery and Zn²⁺ reduction, we developed sulfonated poly(serinol hexamethylene urea) nanoparticles (S-PSHU NPs) co-loaded with CNTF, BDNF, and DPA. In vitro release studies demonstrated sustained release of CNTF and BDNF for up to 8 weeks and DPA for up to 4 weeks. In a rat optic nerve crush (ONC) model, DPA-loaded S-PSHU NPs showed dose-dependent elimination of retinal Zn²⁺. Additionally, in primary RGC culture, RGC activity and axon growth correlated with CNTF and BDNF dosage. In vivo, NTF-DPA-loaded S-PSHU NPs significantly enhanced RGC survival and axon protection post-ONC, as evidenced by cholera toxin subunit B (CTB)-labeled axons in the central visual centers of the brain, including the suprachiasmatic nucleus, lateral geniculate nucleus, and superior colliculus.</div></div><div><h3>Statement of significance</h3><div>• Co-delivery of neurotrophic factors (NTFs: CNTF and BDNF) and a zinc chelator (dipicolylamine, DPA) promotes retinal ganglion cell (RGC) axon survival and protection.</div><div>• Sustained release of NTFs for up to 8 weeks and DPA for up to 4 weeks.</div><div>• DPA-loaded nanoparticles effectively eliminate excess retinal zinc after optic nerve injury.</div><div>• NTF-DPA-loaded nanoparticles significantly improve RGC survival and axon protection in a rat optic nerve crush model.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 297-308"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Property-tailoring chemical modifications of hyaluronic acid for regenerative medicine applications","authors":"Peiling Huang ,&nbsp;Li Wang ,&nbsp;Boon Chin Heng ,&nbsp;Ismaeil Haririan ,&nbsp;Qing Cai ,&nbsp;Zigang Ge","doi":"10.1016/j.actbio.2025.06.014","DOIUrl":"10.1016/j.actbio.2025.06.014","url":null,"abstract":"<div><div>Hyaluronic acid (HA) as well as HA-based materials are widely applied in regenerative medicine due to their good biocompatibility, bioactivity and amenability to chemical modifications. Although the reactive sites and associated reaction types of HA have been summarized previously to guide chemical modification and synthesis of HA-based materials, the relationship between chemical modifications and HA-based material properties has not yet been discussed. In this review, the key properties of HA-based materials required for regenerative medicine in various tissues and organs including skin, bone, cartilage, heart and cornea are summarized and various chemical modification strategies aimed at achieving these properties are discussed. Versatile HA-based materials can be tailored through crosslinking and conjugation, as well as regulating the internal bonding types and degrees of modification. We also provide a comparative analysis of commonly used HA-based materials modification methods and discuss their practical advantages, limitations, and the current status of clinical translation. Even with significant progress already achieved, there is still a long way to go in precisely fine-tuning chemical modifications, balancing functionality and practicality, as well as in understanding their interactions with the diverse array of cells and tissues <em>in vivo</em>. This review bridges tissue-specific property demands with chemical design strategies. We believe that this demand-driven framework provides a practical and accessible guide for researchers intending to design HA-based materials with targeted regenerative capabilities.</div></div><div><h3>Statement of significance</h3><div>This review critically examines hyaluronic acid (HA) and HA-based materials in regenerative medicine applications, focusing on the key properties required for applications in specific tissues such as skin, bone, cartilage, heart, and cornea, as well as the associated chemical modification strategies. While design strategies for HA-based materials have been studied in the past, the relationship between chemical modifications and the resulting material properties remains under-explored. This review thus addresses this gap by systematically categorizing various chemical modification strategies that have been tailored to different material property requirements, providing a comparative analysis of commonly used chemical modification methods, and discussing current clinical challenges and future directions of HA-based materials. By linking material properties to chemical modification strategies, this review thus provides a comprehensive guide for researchers and offers valuable insights for advancing the applications of HA-based materials in regenerative medicine.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 75-100"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discoidal nanoparticles exploit thrombus-induced shear gradients to enhance site-specific thrombolysis in stroke","authors":"Chunping Liu ,&nbsp;Jiaoyang Wang ,&nbsp;Zhenhua Wang ,&nbsp;Xinyu Fan ,&nbsp;Jingmei Pan ,&nbsp;Xing Guo ,&nbsp;Shaobing Zhou","doi":"10.1016/j.actbio.2025.06.027","DOIUrl":"10.1016/j.actbio.2025.06.027","url":null,"abstract":"<div><div>Thromboembolic stroke is characterized by cerebral ischemia caused by arterial thrombosis. Although tissue plasminogen activator (tPA) remains the gold standard for thrombolytic therapy, its clinical use is limited by a narrow therapeutic window and the need for continuous infusion. Nanoparticle-based delivery platforms have been explored to enhance the thrombolytic performance of tPA; however, efficient targeting to thrombus sites remains a key challenge. Notably, thrombosis-induced alterations in blood flow shear stress significantly influence the margination behavior of nanoparticles, which is highly dependent on their morphology and directly impacts thrombus accumulation and lytic efficacy. In this study, we fabricated poly (lactic-co-glycolic acid) (PLGA) nanoparticles with spherical, rod-shaped, and discoidal geometries, and conjugated them with tPA. Among these, discoidal nanoparticles (D-tPA) demonstrated enhanced margination and preferential adhesion to thrombi under high shear conditions, leading to improved thrombolysis and restoration of cerebral perfusion. These findings highlight the critical role of particle shape in vascular drug delivery and position discoidal PLGA nanoparticles as a promising strategy for targeted thrombolytic therapy in ischemic stroke.</div></div><div><h3>Statement of significance</h3><div>This study presents the application of discoidal poly (lactic-co-glycolic acid) (PLGA) nanoparticles for the treatment of thromboembolic stroke, offering an innovative approach to improving drug delivery and thrombolytic efficiency. Compared to spherical or rod-shaped nanoparticles, discoidal nanoparticles exhibit significant margination and thrombus adhesion under high shear stress conditions, thereby enhancing thrombolysis and promoting blood flow restoration. This work opens new avenues for nanomedicine in stroke therapy and holds potential clinical significance for more effective and targeted treatments in vascular diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 471-484"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nano-based therapy for type 1 diabetes: from immuno-intervention to insulin delivery","authors":"Huiwen Pang,&nbsp;Zhuo Chen,&nbsp;Felicity Y. Han","doi":"10.1016/j.actbio.2025.06.016","DOIUrl":"10.1016/j.actbio.2025.06.016","url":null,"abstract":"<div><div>Type 1 diabetes (T1D) is a chronic autoimmune disease in which the immune system mistakenly attacks and destroys insulin-producing β-cells in the pancreas, causing an absolute insulin deficiency. While traditional treatments, such as insulin replacement therapy, can alleviate symptoms, they fail to halt disease progression fundamentally. Recent advancements in nanotechnology have shown significant progress in treating T1D, particularly in restoring immune tolerance and enabling precise drug delivery. These innovative nano-based therapies allow researchers to better regulate immune responses and protect the remaining β-cell function. Additionally, breakthroughs in insulin delivery using nano-based systems, including oral, transdermal, and glucose-responsive insulin release delivery systems, have provided new avenues for improving glycemic control in T1D patients. Here by exploring the pathogenesis of T1D and the importance of immune tolerance with the intervention of nanotechnology, this review summarizes nano-based innovative strategies in immune intervention, including antigen, antibody and gene therapy, as well as nano-based insulin delivery systems including the to-date achievement and related challenges remaining. Developing more effective nano-based therapeutic approaches for T1D holds big promise.</div></div><div><h3>Statement of significance</h3><div>T1D remains a significant clinical challenge due to its autoimmune nature and the lifelong dependence on insulin therapy. Traditional treatments manage symptoms but do not address the underlying immune dysfunction. This review underscores the transformative potential of nanotechnology in T1D treatment by integrating immune modulation and advanced insulin delivery. Nano-based immunotherapies aim to restore immune tolerance and preserve β-cell function, tackling the root cause of the disease. At the same time, precise insulin delivery systems offer improved glycemic control with reduced patient burden. By presenting current progress and remaining challenges, this review highlights how nano-based therapies could revolutionize T1D management, offering not only better disease control but also a pathway toward long-term remission and potentially a cure.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 101-120"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homocysteine leads to aortic stiffening in a rabbit model of atherosclerosis","authors":"Francesca Bogoni ,&nbsp;Markus S. Brunner ,&nbsp;Gunter Almer ,&nbsp;Gerd Hörl ,&nbsp;Yuriy G. Tehlivets ,&nbsp;Gerhard Sommer ,&nbsp;Oksana Tehlivets ,&nbsp;Gerhard A. Holzapfel","doi":"10.1016/j.actbio.2025.06.003","DOIUrl":"10.1016/j.actbio.2025.06.003","url":null,"abstract":"<div><div>Hyperhomocysteinemia, an elevated level of homocysteine in the blood, is an independent risk factor for atherosclerosis and, more generally, cardiovascular disease. However, its relationship with aortic biomechanics has not been investigated yet. To better understand the influence of elevated homocysteine levels on aortic biomechanics, we propose an animal model in which hyperhomocysteinemia, hypercholesterolemia, and their combination were induced in rabbits by balloon injury of the abdominal aorta, special diets, and intravenous homocysteine injections. The effects of a diet deficient in B vitamins and choline, which are required for homocysteine degradation, a cholesterol-rich diet, their combination, and increased homocysteine concentration are investigated in relation to abdominal aortic biomechanics in rabbits. For this purpose, equibiaxial and non-equibiaxial extension tests were carried out, and the influence of risk factors on the stress–stretch relationship, mechanical anisotropy, and tissue inelasticity is discussed. The mechanical characterization of the tissue was supported by microstructural histological analyses. Our study reveals that deficiency of B vitamins and choline cause aortic stiffening even in the absence of hypercholesterolemia, suggesting a possible independent role in the development of atherosclerosis. Further increasing homocysteine concentration through intravenous injections in rabbits fed B vitamins and choline-deficient diet also results in a stiffer stress response and more pronounced inelastic phenomena with respect to the control group.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 412-428"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyanhydride nanoparticles encapsulating innate sensor agonists activate epithelial and airway cells and reduce Respiratory Syncytial Virus infection in mice","authors":"Fabián E. Díaz ,&nbsp;Elizabeth A. Grego ,&nbsp;Ali Uslu ,&nbsp;Balaji Narasimhan ,&nbsp;Jodi L. McGill","doi":"10.1016/j.actbio.2025.05.061","DOIUrl":"10.1016/j.actbio.2025.05.061","url":null,"abstract":"<div><div>Acute respiratory tract infections (ARTI) are a leading cause of morbidity and mortality in infants worldwide. Considering the emergence of antimicrobial resistance as a global threat, there is increasing interest in immunomodulatory strategies to prevent respiratory infections. Since ARTIs are caused by several pathogens, immunomodulatory strategies aiming to engage innate responses represent a promising strategy to prevent ARTIs. Here, innate-stimulating nanoparticles (NPs) synthesized from combinations of polyanhydride copolymers and pattern recognition receptor (PRR) agonists were developed to increase disease resistance by activating innate mechanisms at the mucosal level. In vitro analysis on human and bovine respiratory epithelial cells showed that innate-sensor agonist-loaded NPs triggered transcription of inflammatory, antiviral, and antimicrobial mediators. Moreover, pre-treatment with NPs reduced human and bovine orthopneumovirus (RSV) infectious titers in vitro. Intranasal administration of PRR-containing polyanhydride NPs to mice led to transient production of cytokines and chemokines in lungs, suggesting immune activation. The immunogenicity and antiviral properties of NPs were dependent on both polyanhydride copolymer chemistry and the innate agonist encapsulated within the NPs. Prophylactic administration of NPs containing either TLR2/1, TLR4, or TLR2/7 agonists resulted in reduced RSV morbidity and viral lung loads. Selected NPs also showed protective effects when administered 14 days before infection. These results indicate that NPs efficiently prime human and bovine respiratory tract epithelial cells and trigger antiviral defenses in vitro and reduce RSV disease in mice.</div></div><div><h3>Statement of significance</h3><div>Our research focuses on the use of polyanhydride nanoparticles (NPs) encapsulating innate sensor agonists to activate epithelial and airway cells. This innovative approach leverages the unique properties of nanotechnology to harness the innate immune system’s potential, providing broad resistance against multiple pathogens. We designed a panel of PRR agonist-loaded polyanhydride NPs with varying chemistries and investigated their effectiveness as innate immunomodulators in the respiratory tract. We demonstrate that NPs activate protective innate immune responses in airway epithelial cells and reduce RSV infectious titers in vitro. NP-treated mice showed protection against RSV-induced morbidity and had reduced viral loads. These findings highlight the potential of polyanhydride NPs as a versatile platform for prophylactic intervention against respiratory viruses in both humans and livestock.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 501-516"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “AKR1B10 (Aldo-keto reductase family 1 B10) promotes brain metastasis of lung cancer cells in a multi-organ microfluidic chip model” [Acta Biomaterialia 2019, 91, 195-208]","authors":"Wenwen Liu ,&nbsp;Jing Song ,&nbsp;Xiaohui Du ,&nbsp;Yang Zhou ,&nbsp;Yang Li ,&nbsp;Rui Li ,&nbsp;Li Lyu ,&nbsp;Yeting He ,&nbsp;Junxia Hao ,&nbsp;Jing Ben ,&nbsp;Wei Wang ,&nbsp;Haibin Shi ,&nbsp;Qi Wang","doi":"10.1016/j.actbio.2025.05.004","DOIUrl":"10.1016/j.actbio.2025.05.004","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 704-706"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Janus hydrogels delivering low-density lipoprotein receptor-related protein 6 inhibitor enhance myocardial repair via m6A-dependent cuproptosis in bama pigs","authors":"Feila Liu ,&nbsp;Tingting Liang ,&nbsp;Jun Liu ,&nbsp;Peng Qu ,&nbsp;Shiqi Han ,&nbsp;Dayu Sun ,&nbsp;Yansha Hao ,&nbsp;Yue Zhou ,&nbsp;Xue Li ,&nbsp;Cui Ma ,&nbsp;Hongyan Zhang ,&nbsp;Yunbo Luo ,&nbsp;Yali Wang ,&nbsp;Ju Tan ,&nbsp;Qian Lei ,&nbsp;Chuhong Zhu ,&nbsp;Panke Cheng","doi":"10.1016/j.actbio.2025.06.018","DOIUrl":"10.1016/j.actbio.2025.06.018","url":null,"abstract":"<div><div>Copper overload induces a unique form of cell death called <em>cuproptosis</em> via mitochondrial ROS accumulation. Following myocardial infarction (MI), copper ion levels rise significantly in infarcted tissue. Cardiomyocytes, highly sensitive to copper, respond through activation and nuclear translocation of LRP6, which interacts with ALKBH5 to suppress m6A modification of <em>ferredoxin 1 (FDX1)</em>, thereby exacerbating copper toxicity. LRP6 also facilitates copper influx, further promoting cuproptosis. High-throughput screening identified chrysin-7-O-glucuronide (C7Og) as a potent LRP6 inhibitor that mitigates cuproptosis without compromising cardiac protective effects. Moreover, a Janus hydrogel enhanced with benzalkonium chloride-modified tannic acid improves tissue adhesion and glucose delivery. A myocardial patch integrating C7Og within this hydrogel significantly reduced infarct size and improved cardiac function in both rat and Bama miniature pig models, highlighting strong translational potential for MI therapy.</div></div><div><h3>Statement of significance</h3><div>This study uncovers a mechanism of copper-induced cell death, termed cuproptosis, in myocardial infarction (MI). It identifies low-density lipoprotein receptor-related protein 6 (LRP6) as a key regulator of copper influx and cuproptosis, revealing a potential target for mitigating copper toxicity in cardiac tissue. Chrysin-7-O-glucuronide (C7Og), a potent LRP6 inhibitor, offers a promising strategy to prevent LRP6-mediated cell death while preserving its protective role in cardiac function. Encapsulating C7Og in a Janus hydrogel enhances its delivery and adhesion, demonstrating significant efficacy in reducing myocardial damage and improving cardiac function in rat and Bama miniature pig models. This work offers new insights into copper homeostasis and presents a potential therapeutic approach for MI treatment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 255-265"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of electrical stimulation generated by self-powered systems for tissue repair","authors":"Mengnan Chai ,&nbsp;Yufan Li ,&nbsp;Yubao Li ,&nbsp;Yi Zuo ,&nbsp;Jidong Li","doi":"10.1016/j.actbio.2025.05.047","DOIUrl":"10.1016/j.actbio.2025.05.047","url":null,"abstract":"<div><div>Bioelectricity plays an important role in tissue repair. Nanogenerators can harvest biomechanical energy and convert it into electrical signals, producing electrical stimulation (ES) for diverse biomedical applications including sensing, tissue repair, cardiac pacing, etc. This review focuses on the overview of the single or multifunctional role of ES generated by self-powered nanogenerators in bone and tendon, nerve, skin, and myocardial tissue repair. Particularly, to elucidate the differential cellular responses and effects on endogenous electric fields between conventional repair and ES-enhanced tissue regeneration, the possible mechanisms by which ES promotes repair in different tissues are summarized. Eventually, the ES parameters and the matching between the type of ES produced by the nanogenerator and the practical application scenario of biological tissue are discussed. The main challenges and future perspectives of nanogenerators in tissue therapy are also proposed, expecting to promote the development of this emerging restoration method.</div></div><div><h3>Statement of significance</h3><div>As miniature devices for tissue repair, self-powered nanogenerators can achieve the ambitious goal of self-supplying energy and efficient tissue repair. This review article details the electrical stimulation generated by self-powered nanogenerators in different tissue repair by simulating and augmenting endogenous bioelectrical signals. Introducing the classification and mechanisms of nanogenerators and reviewing the influence of the electrical stimulation and electric field in bone and tendon, nerve, skin, and myocardial tissue repair. Notably, the possible mechanisms by which electrical stimulation acts on different tissues are concluded. Lastly, the match between types of nanogenerators and different tissues is proposed, and the main challenges and perspectives of nanogenerators in tissue therapy are also discussed.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 1-33"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red blood cell entrapment in thrombi formed under pathological flow: Stiffness and binding antigens impact thrombus morphology and cell distribution","authors":"Anjana Jayaraman ,&nbsp;Junhyuk Kang ,&nbsp;Purvil Jani ,&nbsp;Nicholas L. Abbott ,&nbsp;James F. Antaki ,&nbsp;Brian J. Kirby","doi":"10.1016/j.actbio.2025.05.055","DOIUrl":"10.1016/j.actbio.2025.05.055","url":null,"abstract":"<div><div>Thrombosis, or pathological blood clot formation, is a dangerous and potentially fatal event that is often associated with implanted medical devices. Thrombi are comprised of platelets, plasma proteins, red blood cells (RBCs) and other molecular and cellular components. Extensive research has been conducted on the dynamics of platelet aggregation and deposition; however, the process of RBC entrapment remains under-explored. In this study, we used a microfluidic device and fluorescence microscopy to concurrently image platelets and RBCs during thrombus formation under flow and biomaterial conditions representative of implanted devices. We designed and applied MATLAB algorithms to track thrombi as they grew over time and interrogated thrombus growth and RBC accumulation trends. To probe the contributions of the unique mechanical properties of RBCs, we characterized the influence of induced RBC stiffness on thrombus forming behavior via imaging. To study the binding effects of known RBC surface antigens, we visualized thrombus formation with inhibition of glycoprotein (GP) IIb/IIIa and integrin-associated protein (IAP) respectively. We found that the accumulation and clustering of RBCs within the thrombi exhibited an inverse relationship with stiffness. Fibrillar structures were also present in these thrombi. Stiff RBCs enhanced platelet aggregate growth in all directions. Inhibition of surface binding proteins GPIIb/IIIa and IAP decreased the stability of thrombi. The results show that RBC deformability impacts entrapment location, fibril growth and spatial distribution. In turn, RBC binding stabilizes and anchors aggregates to surfaces. These findings will inform improved device design and multi-phase models of thrombosis that incorporate RBCs.</div></div><div><h3>Statement of significance</h3><div>Thrombosis, the pathological formation of blood clots, is linked to cardiovascular disease and implanted devices. This study explores the mechanisms by which red blood cells (RBCs) become trapped in clots and their impact on clot properties. Using a microfluidic model, we show that RBC stiffness affects their accumulation and distribution within thrombi, influencing thrombus structure and composition. We also find that RBC surface proteins, such as GPIIb/IIIa and integrin-associated protein, contribute to thrombus stability. These findings will enhance thrombosis models and inform research on the interaction between biomaterials, including blood-contacting devices, and biological systems at the cellular and molecular levels.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"201 ","pages":"Pages 336-346"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}